Current HIV Research - Volume 20, Issue 5, 2022

In the last 5 decades, we have witnessed two major pandemics, AIDS caused by the Human Immunodeficiency Virus (HIV) and the CoronaVirus Disease-19 (COVID-19) caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). The emergence of COVID-19 has raised many concerns for researchers, doctors, patients, and other institutions associated with HIV. A lot of debate has persisted on clinical outcomes, the use of antiretrovirals, and vaccines on HIV patients infected with COVID-19. This note attempts to present different aspects of HIV and SARS-CoV-2 across themes like SARS-CoV-2 coinfections in people living with HIV, the psychological impact, treatments, vaccination, etc. We highlight how learnings from the COVID-19 pandemic can help us in tackling the HIV pandemic.

Background: The COVID-19 pandemic determines the functioning of the healthcare system. The epidemic of HIV infection depends heavily on the effectiveness of the health system and its ability to test and deliver prevention and treatment. This study aims to determine the consequences of this pandemic on the development of HIV infection testing in the Czech Republic. Methods: A descriptive cross-sectional study analyzed data for two infectious diseases, HIV (2020 and 2015-2019) and COVID-19 (2020), in the Czech Republic. For the statistical comparison of 2020 with the earlier period, the Incidence Rate Ratio (IRR) and Poisson regression methods were used. Monthly HIV and COVID-19 indicators for 2020 were analyzed using correlation analysis. Results and Discussion: A significant difference was observed only in April (IRR = 0.81; p = 0.046) and July (IRR = 1.27; p = 0.023) between the number of HIV tests performed in each month in 2020 and the control period (average for the same months of the period 2015-2019). Significant differences between the observed periods were further identified for testing reasons. Correlation analysis of the number of tests performed on HIV and COVID-19 after 2020 showed a negative relationship (r = -0.261, p = 0.412). Conclusion: The study did not confirm statistically significant differences between the number of HIV tests performed in the pandemic year 2020 compared to the previous period, except for two months. The incidence and number of newly diagnosed cases did not differ statistically significantly from previous years (2015-2019).

Background: Several algorithms have been developed to predict cardiovascular risk (CVR) over time, however, none of them seem to be accurate when applied to HIV patients. Objective: The aim of this study was to assess plasma inflammatory biomarkers in relation to multiple CVR scores (FRS, ASCVD, PROCAM and the DAD-5 Years-Estimated-Risk) in an Italian cohort of HIV patients undergoing a combined Antiretroviral Therapy (cART). Methods: We enrolled HIV patients undergoing cART without any change in the HIV-related pharmacological therapy over the last 48 weeks. Demographic and anamnestic data were collected, and a biochemical panel including the following biomarkers was collected: CRP, Cystatin-C, microalbuminuria, IL-18, IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN- γ. CVR scores were obtained for each patient and compared to the biochemical panel to assess statistical correlation. Results: 90 Caucasian HIV patients were enrolled. Assessment of CVR scores showed FRS values of 6.98 ± 6.11%, ASCVD 7.18 ± 6.25%, PROCAM 6.7 ± 7.4%, and DAD-5 Years Estimated Risk 3.10 ± 3.41%. We found correlations between the levels of circulating cytokines measured and the cardiovascular risk prediction scores. Conclusion: Our data showed that the values of selected inflammatory biomarkers strongly correlate with the CVR scores, suggesting that they can be employed as reliable predictors of cardiovascular disease in HIV patients. The routine use of selected biomarkers associated with systemic inflammation could be a valid and readily available tool for clinicians to assess and monitor cardiovascular risk in HIV patients.

Background: Several studies reported on periprosthetic infection after primary THA in HIV-positive patients, but very few showed the results of its revision. Objective: The aim was to compare primary and secondary clinical outcomes after revision arthroplasty for hip joint infection in matched groups of HIV-infected and HIV-negative patients. Methods: Using the hospital database, thirteen HIV-positive patients (13 infected hips) and thirteen HIV-negative patients of the matched control group (13 infected hips) were identified and their records were studied retrospectively. They underwent revision surgery aimed at infection arrest and total hip replacement due to infection developed after primary THA or infected spacers. Harris Hip Score, reinfection rate, limb shortening, and definite outcomes were evaluated with Wilcoxon, Mann-Whitney, and Chi-squared tests. Results and Discussion: Spacers with antibiotics were implanted in patients of both groups at the first step of revision, except for one HIV-infected patient who had resection arthroplasty. The mean follow-up was 29.4 ± 2.7 and 33. ± 2.9 months for the HIV-group and control group, respectively. Three patients of the HIV-group completed two-stage revision arthroplasty versus ten patients from the control group. Re-infection rate was higher in the HIV-group. At final follow-ups, the mean HHS was significantly different (53 ± 3.2 points in the HIV-group versus 79.14 ± 3.1 points in the control group) along with limb length discrepancy (3.71 ± 0.43 versus 1.4 ± 0.32). Conclusion: Both primary and secondary clinical outcomes of revision arthroplasty for hip joint infection in HIV-positive patients were significantly worse than in the matched group of HIVnegative patients. Revisions in HIV-positive group resulted in a higher reinfection rate, a small number of definite two-stage revisions, and lower functional scores.

Objective: In this study, we aimed to determine the prevalence and effectors of hyperlipidemia among People Living with HIV/AIDS (PLWHA) and taking second-line Antiretroviral Therapy (ART) using registry data in central China. Methods: We conducted a cross-sectional study and collected information of PLWHA on secondline ART during 2018 from two medical registries. Hyperlipidemia was defined according to the 2016 Chinese guidelines for the management of dyslipidemia in adults. Univariate and multivariate logistic regression analyses were performed to explore the influencing factors of hyperlipidemia. We calculated Odds Ratios (ORs) and 95% Confidence Intervals (CIs). Results: A total of 2886 PLWHA taking second-line ART were included in this study, and 978 (33.9%) had hyperlipidemia. Female patients, those with hyperglycemia, and patients with CD⁴⁺ cell counts >500 cells/μL had a higher prevalence of hyperlipidemia with 37.0%, 49.0%, and 41.3%, respectively. Multivariate analysis showed that CD⁴⁺ cell count 350-500 cells/μL (OR = 1.72, 95% CI: 1.26-2.38), CD⁴⁺ cell count >500 cells/μL (OR = 2.49, 95% CI: 1.85-3.38), and FPG >6.2 mmol/L (OR = 2.08, 95% CI:1.64-2.65) were risk factors for hyperlipidemia. Male sex (OR = 0.72, 95% CI: 0.61-0.85) and Hb <110 g/L (OR = 0.59, 95% CI: 0.45-0.76) were protective factors against hyperlipidemia. Conclusion: PLWHA on second-line ART had a higher prevalence of hyperlipidemia. Gender, CD⁴⁺ cell count, FPG, and hemoglobin were influencing factors of hyperlipidemia.

Background: Although current available medications have increased the quality of life in HIV-infected patients, there are still some shortcomings in HIV treatment arising from viral resistance, drug side effects, and the high cost of medication. Therefore, there is an urgent need for some suitable HIV inhibitors with different mechanisms of action. Gp41, located on the HIV cell surface, plays an important role in the fusion of viral and host cell membranes. With the same structure in different HIV strains, gp41 seems to be a promising target for developing novel HIV fusion inhibitors. Objective: Based on the essential structural elements of gp41 inhibitors, two series of compounds were prepared, and their inhibitory effect on HIV cell growth was investigated. Compared to the known small-molecule gp41 inhibitors, 2-Alkylthio-1-benzylimidazole-5-carboxylic acid (series I) and (E)-4-{[5-(((1-benzyl-1H-1,2,3-triazol-4-yl)methoxyimino)methyl)-2-(alkylthio)-1H-imidazol- 1-yl]methyl}benzoic acid derivatives (series II) were found to have a more flexible skeleton with extra moieties interacting with the gp41 key residues. Methods: In silico drug design approaches, including molecular docking and molecular dynamics simulations, were employed to design these novel compounds prior to preparation. The designed compounds exhibited proper chemical interactions and stable complexes with gp41. Then, the selected candidates were efficiently synthesized, and their anti-HIV-1 and anti-HIV-2 activities, as well as their cellular cytotoxicity in MT-4 cells were determined. Results: None of the compounds belonging to the series I were active against HIV-1 and HIV-2 replication in cell cultures, and most of the compounds in series II exhibited significant cytotoxicity against MT-4 cells in low micromolar concentrations. Conclusion: The smaller molecular structures of the compounds in series I might be responsible for their poor anti-HIV effects. The high toxicity of the series II compounds on the host cell makes it impossible to assess their anti-HIV activities.

Background: TLR3 polymorphisms affect the risk of HIV infection and modify the disease course. Consequently, we analyzed the association of TLR3 polymorphism (rs5743312, rs3775296, and rs3775291) with susceptibility to HIV-1 acquisition and disease progression. Methods: This is a cross-sectional study. Genotyping of TLR3 polymorphisms is completed by utilizing the PCR-RFLP technique in 153 HIV naive subjects and 158 healthy controls. Results: A haplotype is a physical grouping of genomic variants that tend to be inherited together. The TCC haplotype was increased in HIV-infected individuals compared with healthy controls (0.05% versus 0.03%). TLR3 rs3775291CT genotype was associated with the early stage of HIV infection (OR = 2.19, P = 0.04), with a higher occurrence in the advanced stage of HIV infection when contrasted with healthy controls (41.2% versus 32.3%). TLR3 rs3775296 CA genotype was likely to be associated with the intermediate stage of HIV infection (19.5% versus 31.6%, OR = 0.42, P = 0.06). TLR3 rs5743312TT genotype was more prevalent in the advanced stage of HIV infection compared with healthy controls (2.9% versus 1.9%). TLR3 rs3775296CA genotype was less prevalent in HIV subjects devouring tobacco when contrasted with non-users (9.1% versus 34.9%, OR = 0.25, P = 0.09). TLR3 rs3775296AA and rs3775291CT and TT genotypes have been overrepresented in HIV subjects using alcohol when contrasted with non-users (5.6% versus 1.1%, OR = 1.83, P = 0.67; 50.0% versus 42.2%, OR = 1.84, P = 0.31; 5.6% versus 3.3%, OR = 2.70, P = 0.50). In the multivariate examination, the rs5743312TT genotype showed a greater risk for HIV infection (OR = 1.86, P = 0.50). Conclusion: TLR3 rs3775291 C/T polymorphism may assist the risk of disease progression in alcohol consumers. TLR3 rs3775291 CT genotype may enhance the disease progression, whereas the TLR3 rs3775296 CA genotype may protect against disease progression.

Background: Studies have found that HIV is mainly transmitted through the mucosal surface, and the entrance of early progression of the disease is the rectal and colonic mucosa. So, this paper aimed to explore and analyze the structural differences of gut microbiome between men who have sex with men (MSM) and those who don’t have sex with men (Non-MSM), expecting to find novel biological factors that potentially impact transmission and/or disease in MSM population. Methods: We collected a total of 33 stool samples, 16 were MSM and 17 were Non-MSM. The 16S rRNA gene amplification sequencing was used to detect the alteration and structure of the gut microbiome community in two groups. Results: The difference in β diversity of gut microbiome of two groups of subjects was statistically significant (P<0.001), indicating that the difference in the structure of the gut microbiome of two groups was statistically significant. Compared with the phylum and genus level of Non-MSM group, the relative abundances of Actinobacteria, Proteobacteria, genera Collinsella, Prevotella, Bifidobacterium and Ralstonia in MSM group were higher (P<0.001, P<0.05, LDA score (log10)>2), and the relative abundance of Bacteroidetes, genera Erysipelotrichaceae incertae sedis, Bilophila, Holdemania, Clostridium XIVb and Bacteroidaceae in MSM group were lower (P<0.01, LDA score (log10)>2). Conclusion: There are some differences in the structure of gut microbiome between MSM group and Non-MSM group. It indicates the differences in behavior and characteristics between MSM and Non-MSM populations may be related to the difference in the structure of gut microbiome.

Introduction: Accurate evaluation of the survival rate among HIV-positive populations is pivotal for HIV management. Objective: This study aimed to investigate the survival rate and potential survival-related factors in HIV/AIDS patients from 2011 to 2019 in the city of Kermanshah in the west of Iran. Methods: In this study, 915 HIV-positive patients registered by the Kermanshah Behavioral diseases counseling center were surveyed from 2011 to 2019. The proper data on the survival factors were extracted and statistically analyzed by reading the patients' files. Results: Of 915 patients, 220 (24%) died. The one-year, five-year, and ten-year survival rates were 84%, 72%, and 62%, respectively. There was a significant relationship between the survival rate and many other parameters, including treatment variables, CD⁴⁺ T cell count, the way of HIV transmission, level of education, gender, and marital status. Over time, the timely initiation of treatment has increased. The data also showed that HIV transmission through drug injection has decreased, while the sexual transmission of HIV has increased. Conclusion: The results showed that the survival rate of HIV patients has increased in recent years due to the appropriate treatment. The highest risk factor of death was for people with low CD⁴⁺ T cell count, lack of antiretroviral therapy, low level of education, male gender, and people who inject drugs. These people need more attention to get tested for HIV- related indexes and to receive proper treatment.